The aim of the present study was to examine topoisomerase II alpha (topo II alpha) expression in cancers of the head and neck and to establish a correlation with clinicopathological parameters and survival. Paraffin embedded tissue specimens (studied by immunohistochemistry), from 103 consecutive patients with squamous cell carcinoma of the head and neck regions, were examined on the primary tumor (96 patients) and on recurrence (7 patients). Immunostaining evaluation was quantified by examining at least 1,000 neoplastic cells and counting the percentage of positively stained nuclei. Topoisomerase II alpha expression was correlated with age, gender, stage, site of the disease, tumor differentiation, response to chemotherapy, disease-free survival and overall survival. More than half of the specimens had a high expression of topoisomerase II alpha (> or = 15% positive neoplastic cells). Topoisomerase II alpha expression was significantly higher in tumors of low and moderate differentiation versus tumors of high differentiation (P = 0.00001). There was also a significant difference in topo II alpha in specimens of responders to chemotherapy versus non-responders (P = 0.02), although the cytotoxic drugs used do not belong to topoisomerase II alpha antagonists. The correlation of high topoisomerase II alpha expression and stage of disease, age, gender, primary site, recurrence, disease-free survival and overall survival was not statistically significant. In conclusion, topoisomerase II alpha is highly expressed in histological specimens of the majority of patients with head and neck cancers; mainly, it is related to a significant degree to low and moderately differentiated tumors versus highly differentiated ones. High expression of topoisomerase II alpha is also significantly related to response to chemotherapy.